Cognition, Tobacco Smoke and Nicotinic Receptor Occupancy Tobacco smoking has beneficial effects on cognition. In some cases smoking improves cognitive performance and in others it reverses deficits brought on by smoking deprivation. Many of the cognitive enhancing effects of smoking have been attributed to the pharmacological actions of nicotine on nicotinic acetylcholine receptors (nAChR). Nicotine improves performance on working memory tasks, motor response tests of focused and sustained attention and recognition memory. In addition to nicotine, tobacco smoke includes approximately 4000 additional compounds, of which many are pharmacologically active and may contribute to the effects of smoking on cognition. The cognitive effects of nicotine versus tobacco smoke have not yet been delineated. Moreover it is not clear how the degree of nicotine occupancy of brain nicotinic acetylcholine receptors (nAChR ) is correlated with cognitive performance. In the present study we propose to explore the effects of tobacco smoke, denicotinized tobacco smoke and nicotine on performance on cognitive tasks of attention, learning, memory, speed of information processing and executive functions in smokers while they are actively smoking; after 12 -24 h abstinence; after 7 days abstinence and after smoking a nicotine-containing cigarette; a de-nicotinized cigarette and after using the nicotine inhaler. The relationship between cognitive performance and the number of brain (32-nAChR and the amount of nicotine delivered to cortical and subcortical brain areas will be measured using [123I] 5-IA-85380 and SPECT. These exploratory studies will delineate the role of nicotine versus denicotinized tobacco smoke on cognitive performance in acutely abstinent smokers. In addition they will provide critical information about the interaction of nicotine with p2-nAChR and the relationship to improvements in cognitive performance. [unreadable] [unreadable] [unreadable]